1. Field of the Invention
The invention relates generally to an oral composition having a function in lubricating the mouth and preventing the formation of stains on the surfaces of the teeth. The active ingredients of the composition are a polyvinyl alcohol and a metal chelating agent.
The invention also encompasses a method of treating xerostomia comprising of administering to an affected individual a lubricant composition containing an alcoholic polymer and a metal chelating agent in an orally acceptable vehicle.
2. The Prior Art
Xerostomia commonly known as “dry mouth” is a condition in which the salivary glands do not produce sufficient quantities of saliva. This causes discomfort that can in some cases be quite severe. Without saliva, the mouth burns and the throat and tongue can undergo physiological changes. Teeth can also decay rapidly and the tongue can become smooth, cracked and vulnerable to infection.
The mouth is one of the body areas most exposed to the external environment. Normally, mucous forms a continuous protective layer in the nose, mouth and throat. A patient suffering from xerostomia not only has decreased fluid in the mouth, but also an insufficient quantity of mucoproteins and mucopolysaccharides to hold fluid in contact with the cells and create a barrier to irritation and infection.
Cases of xerostomia may vary from the mild, in which only slight dryness is experienced, to severe cases in which the patient will have serious problems with mastication, swallowing, digestion, speech, and the like. As noted in U.S. Pat. No. 4,438,100 to Balslev et al., there is a number of causes of xerostomia, including the physiological (e.g., age, menopause, postoperative conditions, dehydration), as well as the psychological (nervousness). The reasons for mouth dryness may also be pharmacological (e.g., as a common side effect of many medications, including anti hypertensives, diuretics, anti-arthritics and anti-depressants) or as a result of radiotherapy. The most severe cases of xerostomia are caused by radiation therapy after head and neck surgery and by autoimmune diseases such as lupus, Sjogrens Syndrome, and rheumatoid arthritis.
Until recently, the treatments for xerostomia have had significant drawbacks. For example, symptoms of mild xerostomia can be somewhat alleviated by consumption of fluids, hard candy and throat lozenges. Because of the susceptibility of xerostomia patients to tooth decay and gum disease, however, the increased sugar intake associated with conventional candy and lozenges is of real concern. In addition, fluids or candy are typically not effective with more severe cases of xerostomia, nor do they provide long-lasting relief with mild cases.
Artificial saliva and salivary substitutes have been proposed as palliative treatments for the symptoms of xerostomia, which preparations have physical and chemical properties that simulate those of natural (human) saliva.
Artificial salvias of the prior art include compositions, which contain ions that mimic those found in natural saliva; glycerin, as well as carboxymethylcellulose-based preparations to provide the proper level of viscosity. Fluoride ions are sometimes included to prevent demineralization of tooth enamel. These compositions have not found wide acceptance as many patients find, that such preparations are irritating or distasteful, and that their lubricating effect is of relatively short duration. This lack of wide acceptance is believed due, at least in part to the fact that the artificial saliva preparations of the prior art do not fully possess the rheological characteristics of natural saliva which are responsible for natural saliva's lubricating effect. An article entitled “Lubrication and Viscosity Features of Human Saliva and Commercially Available Saliva Substitutes”, M. N. Hatton et al, J. Oral Maxillotac. Surg. 45, 496-499 (1987), contains a full discussion of the problems associated with the presently available commercial saliva substitutes in the treatment of individuals with diminished salivary gland function.
In view of the problems, which occur when salivary secretion is deficient, it will be understood that it would be most desirable to have an oral lubricating composition for human use, to relieve the above-mentioned discomforts and inconveniences incurred by xerostomia or by a greater or lesser tendency to dryness of the mouth. Such a composition should have lubricating properties which are as close to the properties of the natural saliva so as to provide to the patient long-term relief from the symptoms of xerostomia or dry mouth.
The uses of lubricating polymers are well known the ophthalmic area. For example, U.S. Pat. No. 4,529,535 to Sherman discloses a rewetting solution that is particularly useful for rigid silicone copolymer contact lenses, including extended wear lenses. In one embodiment, the rewetting solution contains the combination of hydroxyethylcellulose, polyvinyl alcohol, and polyvinylpyrrolidone. U.S. Pat. No. 4,748,189 to Su et al. discloses ophthalmic solutions for improving the exchange of fluid in the area outside a hydrogel contact lens in the area underneath the hydrogel contact lens, in order to permit tear exchange to occur, thereby preventing the accumulation of waste matter and debris under the lens. The solution contains a hydrogel-flattening agent, for example urea, glycerin, propylene glycol, sorbitol, or an amino-ethanol. Surfactants that are useful in the solution include poloxamer and tyloxapol. Suitable lubricants include hydroxylethylcellulose, polyvinylalchol, and polyvinylpyrrolidone.
For a lubricating polymer to be useful in the oral cavity it should be non-irritating and have adhesive properties. Various polymers have been proposed for use in establishing adhesive contact with mucosal surfaces. See, for example, Biegajski, U.S. Pat. No. 5,700,478 to Lowey, U.S. Pat. No. 4,259,314 to Lowey, U.S. Pat. No. 4,680,323 to Yukimatsu et al., U.S. Pat. No. 4,740,365 to Kwiatek et al., U.S. Pat. No. 4,573,996 to Suzuki et al., U.S. Pat. No. 4,292,299 to Suzuki et al., U.S. Pat. No. 4,715,369 to Mizobuchi et al., U.S. Pat. No. 4,876,092 to Fankhauser et al, U.S. Pat. No. 4,855,142; Nagai et al., U.S. Pat. No. 4,250,163 to Nagai et al., U.S. Pat. No. 4,226,848 to Browning, U.S. Pat. No. 4,948,580 to Schiraldi et al. Typically, these adhesives consist of a matrix of a hydrophilic, e.g., water soluble or swell able, polymer or mixture of polymers which can adhere to wet mucosal surfaces. Such polymers are inclusive of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxy ethylcellulose, ethylcellulose, carboxymethyl cellulose, dextran, gaur-gum, polyvinyl pyrrolidone, pectins, starches, gelatin, casein, acrylic acid, acrylic acid esters, acrylic acid copolymers, vinyl polymers, vinyl copolymers, vinyl alcohols, alkoxy polymers, polyethylene oxide polymers, polyethers, and the like. These adhesives may be formulated as ointments, thin films, tablets, troches, and other forms. Often, these adhesives have had medicaments mixed therewith to effectuate slow release or local delivery of a drug rather then treat xerostomia or dry mouth.
Some of the polymers described above have several drawbacks. For example materials such as Carbopol (carboxyvinyl polymers), are not water soluble thus leave a tacky, greasy residue in the oral cavity of the wearer, and can cause sustained oral irritation and some forms of adhesives remain in the oral cavity for only short periods of time, e.g. generally not more than about 10 or 20 minutes, and therefore cannot provide for delivery of a substance over an extended period of time.
U.S. Pat. No. 5,886,054 discloses a composition to treat xerostomia, which comprises of an aqueous solution of at least one polymer and at least one electrolyte, wherein the aqueous solution is preferably buffered and optionally contains at least one mucin. The polymer can be chosen for instance from the group which consists of scleroglucan, guar gum, xanthan gum, sodium carboxymethyl cellulose, hydroxyethyl cellulose, polyacrylic acid and polyvinyl alcohol. The therapeutic composition according to the invention can serve as saliva substitution agent, artificial tear water, in a mouth rinse or in a toothpaste. The aforementioned patient teaches that the mucin is critical because saliva mucins can adhere to both the surface of the teeth and to the oral mucosa and polyacrylic acid subsequently binds to the mucin in order to form a protective layer.
For a lubricant to be effective, it has to interact with the surfaces it is protecting. Referring to U.S. Pat. No. 5,886,054, the disadvantage of combining polyvinyl alcohol with an electrolyte is that the cation may interact with the polymer and cause precipitation of polyvinyl alcohol. Further, saliva is known to contain high concentrations of electrolytes, which may cause further precipitation of polyvinyl alcohol thus leaving a granular feeling in the mouth. Hence, the addition of a metal chelating agent to a formulation containing polyvinyl alcohol will aid in its anti-xerostomia properties. Further inclusion of salivary mucins have other disadvantages including; the mucins are biopolymers which are difficult to obtain in sufficient quantities and suitable purity, they are expensive and they may be obtained from animal salivary glands which may make the use of mucin unsuitable for some consumers and patients. Hence, there is a need to develop products that will retain moisture in the oral cavity that will be inexpensive, and will be acceptable to a majority of consumers. It will also be beneficial to develop products that have added benefits such as prevention of dental stains or accumulation of unaesthetic materials on tooth surfaces and also to prevent irritation/inflammation occurring as a result of dry mouth.